Modulation of functional and biochemical activities of macrophages have been examined. We have demonstrated that macrophages become cytolytic upon in vitro and in vivo treatment with lymphokines, endotoxin or poly I:C. However, lymphokine can induce also a suppressor activity, while poly I:C activated macrophages do not alter the lymphocyte reactivity. We showed that activation for cytotoxicity is associated with a reduced rate of 3H-uridine incorporation by macrophages and we proved that this decrease is due to inhibition of RNA synthesis. Actinomycin D, a specific inhibitor of RNA synthesis, can induce cytotoxic macrophages and at low doses it can synergize with suboptimal amounts of activators to induce cytotoxic activity, suggesting that the decreased role of RNA synthesis and the acquisition of cytotoxic activity may be causally related.